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Meldonium

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1. Jeffrey Aronson: When I Use a Word . . . Meldonium

Jeffrey Aronson: When I Use a Word . . . Meldonium Jeffrey Aronson: When I Use a Word . . . Meldonium - The BMJ ---> Meldonium is in the news again. It was by the World Anti-Doping Agency (WADA) in January 2016 for use by sportsmen and women, because it supposedly increases blood flow and therefore exercise capacity. A few months later, the tennis player was found to have taken it, to “combat a magnesium deficiency, heart problems and because of a family history of diabetes”, and was banned (...) from competition for 15 months. Now, like some others, the Olympic curling bronze medallist Alexander Krushelnitckii (I use the that appears on the back of his Olympic jersey) has also been incriminated. The name “meldonium” goes back to the name of another chemical, ammonium. It starts with a compound IndoEuropean root, BHES-AMADHO, meaning sand, giving the Greek word ψᾰμᾰθος, shortened to ψάμμος. The German pathologist Rudolf Virchow (1821–1902) first used the term “psammoma” in 1900, in a paper

2018 The BMJ Blog

2. The Maria Sharapova drug story: What’s the evidence? Does Meldonium treat heart conditions and diabetes?

The Maria Sharapova drug story: What’s the evidence? Does Meldonium treat heart conditions and diabetes? The Maria Sharapova drug story: What’s the evidence? Does Meldonium treat heart conditions and diabetes? | BJSM blog - social media's leading SEM voice by By David Nunan Many have commented on the , and implications following . Few have looked in more depth at the why? The evidence for “why?” in this case falls in to two key areas. First is the evidence that Mildronate (or Meldonium (...) ) is indicated for the conditions Maria was taking it for, to “combat a magnesium deficiency, heart problems and because of a family history of diabetes”. Second, is the question of whether the drug enhances exercise and sporting performance. I will tackle the second issue in my next blog; here I focus on the question: “What is the evidence for Mildronate/Meldonium to treat heart problems (abnormal ECG), indications for diabetes (familial history) and magnesium deficiency in a 17-year-old athlete

2016 British Journal of Sports Medicine Blog

3. Meldonium use by athletes at the Baku 2015 European Games. Adding data to Ms Maria Sharapova’s failed drug test case

Meldonium use by athletes at the Baku 2015 European Games. Adding data to Ms Maria Sharapova’s failed drug test case Meldonium use by athletes at the Baku 2015 European Games. Adding data to Ms Maria Sharapova's failed drug test case | BJSM blog - social media's leading SEM voice by Meldonium use by athletes at the Baku 2015 European Games Corresponding author: Mark Stuart, BPharm, FRPharmS, FFRPS, mstuart@bmj.com Christian Schneider Professor Klaus Steinbach What are the new findings (...) ? There is an alarmingly high prevalence of meldonium use by athletes in sport as demonstrated by the laboratory findings at the Baku 2015 European Games 13 medallists or competition winners were taking meldonium at the time of the Baku 2015 European Games Meldonium use was detected in athletes competing in 15 of the 21 sports during the Baku 2015 European Games As of 1 January 2016, the World Anti-Doping Agency has put meldonium on the 2016 List of Prohibited Substances and so it is now banned in sport. Meldonium

2016 British Journal of Sports Medicine Blog

4. [Effects of Meldonium in Early Postmyocardial Infarction Period]. (PubMed)

[Effects of Meldonium in Early Postmyocardial Infarction Period]. The aim of PMICS (Postmyocardial Infarction Cardiosclerosis) patients therapy within the dispensary supervision is CCI (Chronic Cardio Insufficiency) progression prevention, life quality improvement, hospitalization number decrease and life prognosis improvement. Despite the developed approaches to the given patients treatment, CCI progression prevention, the main disease treatment ensuring and prognosis assessment are not always (...) as much as possible effective. The search of methods improving the given patients prognosis is highly actual.To evaluate the meldonium clinical effectiveness in the early postmyocardial infarction period.67 patients were included in investigation, their age ranged from 40 to 70. They survived myocardial infarction (MI) and were discharged for further ambulatory supervision. The patients were randomized into two groups: the first one consisting of 32 patients got basic therapy for ischemic heart

2016 Kardiologiia

5. Meldonium and the Prohibited List (PubMed)

Meldonium and the Prohibited List 27350119 2016 06 28 2018 11 13 0312-8008 39 3 2016 Jun Australian prescriber Aust Prescr Meldonium and the Prohibited List. 102 10.18773/austprescr.2016.032 Hughes David D Chief medical officer, Australian Institute of Sport. eng Comment Journal Article 2016 04 07 Australia Aust Prescr 7804938 0312-8008 Aust Prescr. 2015 Oct;38(5):167-70 26648655 Mildronate drug abuse meldonium sports activity 2016 6 29 6 0 2016 6 29 6 0 2016 6 29 6 1 ppublish 27350119 10.18773

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2016 Australian Prescriber

6. Misuse of the metabolic modulator meldonium in sports (PubMed)

Misuse of the metabolic modulator meldonium in sports 30356593 2018 11 14 2213-2961 6 1 2017 Mar Journal of sport and health science J Sport Health Sci Misuse of the metabolic modulator meldonium in sports. 49-51 10.1016/j.jshs.2016.06.008 Lippi Giuseppe G Section of Clinical Biochemistry, University Hospital of Verona, Verona 37134, Italy. Mattiuzzi Camilla C Medical Direction, General Hospital of Trento, Trento 38121, Italy. eng Journal Article 2016 06 24 China J Sport Health Sci 101606001

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2016 Journal of sport and health science

7. [Efficiency of meldonium in the complex therapy of acute coronary syndrome]. (PubMed)

[Efficiency of meldonium in the complex therapy of acute coronary syndrome]. We examined 140 patients (mean age 54.8±3.1 years) with ST elevation acute coronary syndrome resulting in Q-wave myocardial infarction of the left ventricle. From the first hours complex therapy of these patients comprised meldonium (1 g/day intravenously for 2 weeks then orally until 1.5 months). Therapy with meldonium accelerated restoration of left ventricular diastolic function what was in agreement with lowering (...) of NT-proBNT concentration in blood. It was established that administration of meldonium led to reduction of number of high grade ventricular extrasystoles during first 6 hours after thrombolysis, to lowering of blood concentration of lipoperoxide degradation products. Early use of meldonium decreases probability of emergence of fatal arrhythmias and improves prognosis of hospital stage of rehabilitation of patients with acute coronary syndrome resulting in Q-wave myocardial infarction.

2015 Kardiologiia

8. Meldonium use by athletes at the Baku 2015 European Games. (PubMed)

Meldonium use by athletes at the Baku 2015 European Games. The aim of this report was to estimate the prevalence of meldonium use in athletes competing in the Baku 2015 European Games to contribute to the surveillance of substances on the 2015 World Anti-Doping Agency (WADA) Monitoring Program. Meldonium is reported to be used by athletes to potentially enhance personal performance and shorten the recovery period after physical activity.Three sources of data were reviewed to determine (...) the prevalence of meldonium use during the Games including: (1) athlete self-reported declarations of drug and supplement use; (2) declarations from National Olympic Committee medical teams of the list of medicines that they imported into Azerbaijan as part of their stock of drugs for administration; (3) results from the antidoping laboratories reporting the detection of meldonium.Meldonium was declared as imported into Azerbaijan by 2 of 50 National Olympic Committee medical teams at the Games, but athletes

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2016 British Journal of Sports Medicine

9. Story behind meldonium-from pharmacology to performance enhancement: a narrative review. (PubMed)

Story behind meldonium-from pharmacology to performance enhancement: a narrative review. Recent reports from the World Anti-Doping Agency (WADA) indicate an alarming prevalence in the use of meldonium among elite athletes. Therefore, in January 2016, meldonium was added to WADA's prohibited list after being monitored since 2015. Meldonium has been shown to have beneficial effects in cardiovascular, neurological and metabolic diseases due to its anti-ischaemic and cardioprotective properties (...) , which are ascribed mainly to its inhibition of ß-oxidation and its activation of glycolysis. Despite its widespread use, there are only a few clinical studies or clinical trials available. Meldonium is registered in most Baltic countries and is easily accessible through the internet with no serious adverse effects reported by the manufacturer so far. Among athletes, meldonium is used with the purpose of increasing recovery rate or exercise performance. The benefit of taking meldonium in view

2016 British Journal of Sports Medicine

10. [The ability to use meldonium as adaptogen in winter in patients with cardiovascular disease]. (PubMed)

[The ability to use meldonium as adaptogen in winter in patients with cardiovascular disease]. Given that the effects of frost can play the role of independent stress factor influencing the course of cardiovascular disease (CVD), it is reasonable to supplementation of drugs that increase the body's resistance to cold stress. Aim: To evaluate the possibility of using meldonium to prevent unwanted seasonal changes in CVD patients in the winter. The study included 49 patients with CVD aged 38-75 (...) years. Patients were randomized into 2 groups: active management (M), in which in addition to the basic therapy received during the winter 3 months meldonium 1000 mg/day, and a control (K). We measured office blood pressure, heart rate, blood chemistry, determination of glycosylation end products (DGP). Filled with a visual analogue scale (VAS) to assess the quality of life (QOL). During frost marked increase in blood glucose (p = 0.02) in group K, persisting throughout the winter, and an increase

2015 Kardiologiia

11. [Use of meldonium in the combination treatment of patients with heart failure in the early postinfarction period]. (PubMed)

[Use of meldonium in the combination treatment of patients with heart failure in the early postinfarction period]. To evaluate the impact of 10-14-day intravenous administration of meldonium as part of combination therapy in patients with chronic heart failure in the early post-infarction period on the recovery period, structural and functional parameters, and heart rate variability (HRV).The investigation enrolled 60 patients (men and women) aged 45 to 75 years at weeks 3-4 after post (...) -myocardial infarction with symptoms of Functional Class II-III heart failure. All the patients underwent 24-hour electrochocardiography monitoring, cardiac echocardiography, and HRV study. After dividing the patients into 2 groups, Group 1 (a study group) (n = 30) was given intravenous meldonium (idrinol) 1000 mg/day in addition to the basic therapy of coronary heart disease. The patients in the study and control (Group 2; n = 30) groups were at baseline matched for age, gender, disease severity

2014 TerapevticheskiÄ­ arkhiv

12. [Cardioprotective Capabilities of Drug Meldonium in Secondary Prevention After Percutaneous Coronary Intervention in Patients With Documented Myocardial Ischemia.] (PubMed)

[Cardioprotective Capabilities of Drug Meldonium in Secondary Prevention After Percutaneous Coronary Intervention in Patients With Documented Myocardial Ischemia.] The purpose of research — analysis of capabilities in cytoprotective drug mеldonium, in complex in the cardioprotective effect of secondary prevention after percutaneous coronary intervention (PCI). Patients with stable coronary heart disease (n=35 ) aged ≤65 years with incomplete revascularization at 6 months after PCI and positive (...) after 10 intense CPT increased to 20.8±1.06 ml/kg/min compared to baseline (18.6±1.1 ml/kg/min, p<0.05) and the control group (18.5±1.5 ml/kg/min, p<0.05). Use of meldonium was also associated with decrease of maximum ST-segment depression (from -0.18±0.1 to 0.10±0.2 mV), increases of exercise duration (from 364±22 to 556±29 s) threshold heart rate (from 118±12 to 132±5 bpm), decrease of time of ST segment recovery to baseline (from 385±32 to 242±22 s, p<0.05). Final level of free fatty acids

2014 Kardiologiia

13. UPLC-MS/MS method for bioequivalence study of oral drugs of meldonium. (PubMed)

UPLC-MS/MS method for bioequivalence study of oral drugs of meldonium. A rapid and simple method based on ultra-performance liquid chromatography on a hydrophilic interaction chromatography column with tandem mass-selective detection (UPLC-MS/MS) to determine meldonium in human plasma was developed. The calibration curve acquired in the range of 10-6000 ng/mL had quadratic form. Method validation proved the conformity of its properties (selectivity, matrix effect, lower limit of quantification (...) , accuracy, precision and recovery) with the established requirements. The stability tests necessary for bioanalytical studies were performed. For the first time, the method was successfully applied to the bioequivalence studies of generic and brand name oral drugs of meldonium in capsules. Based on data from 24 volunteers, it was determined that the mean pharmacokinetic curves of the drugs are characterized by a double peak profile.Copyright © 2011 John Wiley & Sons, Ltd.

2012 Biomedical chromatography : BMC

14. Jeffrey Aronson: When I Use a Word . . . Carnitine

Jeffrey Aronson: When I Use a Word . . . Carnitine Jeffrey Aronson: When I Use a Word . . . Carnitine - The BMJ ---> I discussed meldonium, which was by the World Anti-Doping Agency (WADA) in January 2016 for use by sportsmen and women, because it supposedly increases blood flow and therefore exercise capacity. Meldonium is the International Nonproprietary Name (INN) of 3-(2,2,2-trimethyldiazaniumyl)propanoate, an analogue of the immediate precursor of carnitine, trimethylaminobutyrate (Figure (...) 1). Meldonium is transported by and inhibits an organic cation transporter (OCTN2), which transports carnitine and is also known as . It is therefore retained in muscle tissue during long term treatment, at least in . It also the dioxygenase that converts trimethylaminobutyrate to carnitine. Figure 1. The biosynthesis of carnitine Carnitine is important for the beta-oxidation of fatty acids. Long chain fatty acids in the cytosol have to be transported into mitochondria before they can

2018 The BMJ Blog

15. A fatty acid analogue targeting mitochondria exerts a plasma triacylglycerol lowering effect in rats with impaired carnitine biosynthesis. (PubMed)

A fatty acid analogue targeting mitochondria exerts a plasma triacylglycerol lowering effect in rats with impaired carnitine biosynthesis. L-carnitine is important for the catabolism of long-chain fatty acids in the mitochondria. We investigated how the triacylglycerol (TAG)-lowering drug 2-(tridec-12-yn-1-ylthio)acetic acid (1-triple TTA) influenced lipid metabolism in carnitine-depleted, 3-(2,2,2-trimethylhydrazinium)propionate dehydrate (Mildronate; meldonium)-treated male Wistar rats

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2018 PLoS ONE

16. Mobile app to tackle doping in sport: the ASADA Clean Sport

-doping and the physician’s role: how do we overcome the challenges in elite sport?” BJSM Blogs . FREELink here – Stuart, M. Schneider, C.; Steinbach, K. (2016). “Meldonium use by athletes at the Baku 2015 European Games. Adding data to Ms Maria Sharapova’s failed drug test case” BJSM Blogs . FREELink here – HP Dijkstra, HP; Van Dyk, N; Schumacher, YO (2015). “Can I tell you something? I’m doping…” BJSM Blogs . FREELink here – “The World Anti-Doping Agency, and blood passports, with Alan Vernec” (2013

2018 British Journal of Sports Medicine Blog

17. Rigvir: A cancer "cure" imported from Latvia that cancer patients should avoid

of meldonium (Mildronate) ) [5] keeps asserting without the smallest feeling of guilt that Rigvir is the first-choice agent for the treatment of a “sensitive” tumor [6], even after multiple objections.” Then, like many dubious clinics, the Virotherapy Center disparages conventional medicine and portrays Rigvir as “natural”: Communications expert ( translator’s note: online writer on science and evidence-based medicine ) Ksenija Andrijanova emphasizes that the way the Virotherapy Center advertises itself

2017 Respectful Insolence

18. If Rigvir is effective “virotherapy” for cancer, why are quack clinics selling it and quackery promoters like Ty Bollinger promoting it?

and and has many publications and patents. In contrast, he does not mention that Dr. Kalvins . Googling him, I found that he is best known for developing a heart medication, (generic name: meldonium). Interestingly, although Bollinger claims Kalvins has over 650 publications, I could only find ten in PubMed. In any case, my first thought was: If such a seemingly good “conventional” scientist is behind Rigvir, then why is it that the IVC has not published anything resembling good science supporting its (...) claims for Rigvir? This is not a person who doesn’t know how to publish. Oddly enough, he is not co-author of any of the few publications I could find in PubMed about Rigvir. Less oddly, given his support of Rigvir, he is not well-regarded outside of Latvia, basically because he makes claims for meldonium that are . Indeed, meldonium was the alleged performance-enhancing drug that Russian tennis player Maria Sharapova was , leading to her suspension. Although it is approved in Latvia and several

2017 Respectful Insolence

19. If Rigvir is effective "virotherapy" for cancer, why are quack clinics selling it and quackery promoters like Ty Bollinger promoting it?

and and has many publications and patents. In contrast, he does not mention that Dr. Kalvins . Googling him, I found that he is best known for developing a heart medication, (generic name: meldonium). Interestingly, although Bollinger claims Kalvins has over 650 publications, I could only find ten in PubMed. In any case, my first thought was: If such a seemingly good “conventional” scientist is behind Rigvir, then why is it that the IVC has not published anything resembling good science supporting its (...) claims for Rigvir? This is not a person who doesn’t know how to publish. Oddly enough, he is not co-author of any of the few publications I could find in PubMed about Rigvir. Less oddly, given his support of Rigvir, he is not well-regarded outside of Latvia, basically because he makes claims for meldonium that are . Indeed, meldonium was the alleged performance-enhancing drug that Russian tennis player Maria Sharapova was , leading to her suspension. Although it is approved in Latvia and several

2017 Respectful Insolence

20. If Rigvir is effective “virotherapy” for cancer, why are quack clinics selling it and quackery promoters like Ty Bollinger promoting it?

, for obvious reasons.) In his narration, Bolinger notes that Dr. Kalvins is a member of the European Academy of Sciences and and has many publications and patents. In contrast, he does not mention that Dr. Kalvins . Googling him, I found that he is best known for developing a heart medication, (generic name: meldonium). Interestingly, although Bollinger claims Kalvins has over 650 publications, I could only find ten in PubMed. In any case, my first thought was: If such a seemingly good "conventional (...) " scientist is behind Rigvir, then why is it that the IVC has not published anything resembling good science supporting its claims for Rigvir? This is not a person who doesn't know how to publish. Oddly enough, he is not co-author of any of the few publications I could find in PubMed about Rigvir. Less oddly, given his support of Rigvir, he is not well-regarded outside of Latvia, basically because he makes claims for meldonium that are . Indeed, meldonium was the alleged performance-enhancing drug

2017 Respectful Insolence

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